放松调节的JNK信号增强了高热症期间的亡
Atsushi Enomoto1, Takemichi Fukasawa2,3, Hiroshi Terunuma4
1Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
概括
热能通过降低DUSP16,一种JNK酸酶来激活c-Jun N-终端激酶 (JNK). 这导致ASK1-SEK1-JNK通路的激活和随后的亡,即使上游信号减少.
科学领域:
- 细胞应激反应的细胞应激反应
- 信号传导途径的信号传导途径.
- 细胞亡调节的调节
背景情况:
- c-Jun N-终端激酶 (JNKs) 是一个小基因激活蛋白激酶 (MAPKs) 的子家族,被各种刺激激活.
- 热诱导的JNK激活的精确分子机制在很大程度上仍未被阐明.
- 了解热引起的JNK激活对于理解细胞对热应激反应至关重要.
研究的目的:
- 阐明JNK热诱导激活背后的分子机制.
- 研究上游MAP激酶成员和酸酶在这个过程中的作用.
- 为了澄清导致在高温下JNK激活的途径.
主要方法:
- 西方涂抹测试用于评估在高温下HeLa细胞中MAPK表达水平.
- 在体外激酶测试以评估MAPK成员的活性.
- 通过siRNA介导的敲除来研究特定的MAPK成员和DUSP16在细胞死亡中的作用.
主要成果:
- 高热症降低了MAP3K水平 (ASK1,MLK3),但没有下游的MAP2K/SEK1或MAPK/JNK.
- 基酸化以温度依赖的方式发生,独立于上游MAP3K/MAP2K酸化.
- 在高热后减少DUSP16表达与增强的JNK激活和亡相关.
结论:
- 热量对JNK的激活取决于温度,尽管上游信号减少,但仍会发生.
- 超热引起的DUSP16降解是激活ASK1-SEK1-JNK通路的关键事件.
- 这种途径的激活有助于热引起的亡.
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